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Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial
  1. Seth D Crockett1,
  2. Elizabeth L Barry2,
  3. Leila A Mott2,
  4. Dennis J Ahnen3,
  5. Douglas J Robertson4,
  6. Joseph C Anderson4,
  7. Kristen Wallace5,
  8. Carol A Burke6,
  9. Robert S Bresalier7,
  10. Jane C Figueiredo8,
  11. Dale C Snover9,
  12. John A Baron1
  1. 1 Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
  2. 2 Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, USA
  3. 3 Division of Gastroenterology, University of Colorado School of Medicine, Aurora Health Care, Denver, Colorado, USA
  4. 4 Division of Gastroenterology and Hepatology, VA Medical Center, White River Junction, VT & Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, USA
  5. 5 Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
  6. 6 Department of Gastroenterology, Cleveland Clinic School of Medicine, Cleveland, Ohio, USA
  7. 7 Department of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  8. 8 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  9. 9 Department of Pathology, Fairview Southdale Hospital, Edina, Minnesota, USA
  1. Correspondence to Dr Seth D Crockett, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC 27516, USA; sethc{at}med.unc.edu

Abstract

Objective Serrated lesions such as sessile serrated adenomas or polyps (SSA/Ps) are important colorectal cancer precursors, but aetiological factors for these lesions are largely unknown. We aimed to determine the effects of calcium and vitamin D supplementation on the incidence of serrated polyps (SPs) in general and hyperplastic polyps and SSA/Ps specifically.

Design Participants with one or more adenoma at baseline were randomised to receive 1200 mg/day of elemental calcium, 1000 IU/day of vitamin D3, both or neither agent. Treatment continued for 3 or 5 years, when risk of polyps was determined from surveillance colonoscopy (treatment phase). Outcomes after treatment ceased were also assessed (observational phase). Adjusted risk ratios (aRRs) of SPs were determined via multivariable generalised linear models.

Results SPs were diagnosed in 565 of 2058 (27.5%) participants during the treatment phase and 329/1108 (29.7%) during the observational phase. In total, 211 SSA/Ps were identified during follow-up. In the treatment phase, there was no effect of either calcium or vitamin D on incidence of SSA/Ps. However, during the later observational phase, we observed elevated risks of SSA/Ps associated with calcium alone and calcium+vitamin D treatment (aRR (95% CI): 2.65 (1.43 to 4.91) and 3.81 (1.25 to 11.64), respectively).

Conclusion In a large multicentre chemoprevention study, we found evidence that calcium and vitamin D supplementation increased the risk of SSA/Ps. This appeared to be a late effect: 6–10 years after supplementation began. These possible risks must be weighed against the benefits of calcium and vitamin D supplementation.

Trial registration number NCT00153816; Results.

  • adenoma
  • colon carcinogenesis
  • cancer prevention
  • micronutrients

https://doi.org/10.1136/gutjnl-2017-315242

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    Footnotes

    • Contributors SDC: study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. ELB: acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. LAM: acquisition of data; statistical analysis; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; technical support. DJA: site PI of original study; critical revision of the manuscript for important intellectual content. DJR: clinical director of original study, critical revision of the manuscript for important intellectual content. JCA, KW, CAB, RSB and JCF: critical revision of the manuscript for important intellectual content. DCS: pathologist for original study; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. JAB: study concept and design; obtained funding; administrative and material support; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; study supervision. All authors approved the final draft.

    • Funding This study was funded a grant from the National Institutes of Health, National Cancer Institute (CA098286, PI: Baron). SDC’s effort was supported in part by a grant from the NIH (KL2TR001109).

    • Competing interests None of the authors report conflicts of interest related to this article. Full disclosures are as follows: SDC: Research funding from Exact Sciences, ColoWrap and Boston Scientific. DJA: Scientific Advisory Board for Cancer Prevention Pharmaceuticals, Speakers Bureau for Ambry Genetics. DJR: Scientific Advisory Board for Medtronic and Consultant for Freenome. CAB: Research funding from Cancer Prevention Pharmaceuticals. JAB: Together with Dartmouth College, JAB: holds a use patent for the chemopreventive use of calcium, currently not licensed.

    • Ethics approval Multiple IRBs (multicentre study).

    • Provenance and peer review Not commissioned; externally peer reviewed.